scholarly journals Increased Circulating Cell-Free DNA in Eosinophilic Granulomatosis With Polyangiitis: Implications for Eosinophil Extracellular Traps and Immunothrombosis

2022 ◽  
Vol 12 ◽  
Author(s):  
Teppei Hashimoto ◽  
Shigeharu Ueki ◽  
Yosuke Kamide ◽  
Yui Miyabe ◽  
Mineyo Fukuchi ◽  
...  
Keyword(s):  
Disease Activity ◽  
Clinical Significance ◽  
Platelet Adhesion ◽  
Granulomatosis With Polyangiitis ◽  
Eosinophilic Granulomatosis With Polyangiitis ◽  
Tissue Samples ◽  
Extracellular Traps ◽  
Free Dna ◽  
Eosinophilic Granulomatosis

BackgroundEndogenous DNA derived from nuclei or mitochondria is released into the blood circulation as cell-free DNA (cfDNA) following cell damage or death. cfDNA is associated with various pathological conditions; however, its clinical significance in antineutrophil cytoplasmic antibody-associated vasculitis (AAV) remains unclear. This study aimed to evaluate the clinical significance of cfDNA in AAV.MethodsWe enrolled 35 patients with AAV, including 10 with eosinophilic granulomatosis with polyangiitis (EGPA), 13 with microscopic polyangiitis, and 12 with granulomatosis with polyangiitis. Serum cf-nuclear DNA (cf-nDNA) and cf-mitochondrial DNA (cf-mtDNA) levels were measured by quantitative polymerase chain reaction before and after the initiation of immunosuppressive therapy. Tissue samples from EGPA patients were examined by immunofluorescence and transmission electron microscopy. The structure of eosinophil extracellular traps (EETs) and neutrophil extracellular traps (NETs) and stability against DNase were assessed in vitro. Platelet adhesion of EETs were also assessed.ResultsSerum cf-nDNA and cf-mtDNA levels were significantly higher in AAV than in healthy controls, with the highest levels in EGPA; however, serum DNase activities were comparable among all groups. cf-nDNA and cf-mtDNA decreased after treatment and were associated with disease activity only in EGPA. Blood eosinophil count and plasma D-dimer levels were significantly correlated with cf-nDNA in EGPA and cf-mtDNA. EGPA tissue samples showed lytic eosinophils and EETs in small-vessel thrombi. The structure of EETs showed bolder net-like chromatin threads in vitro and EETs showed greater stability against DNase than NETs. EETs provided a scaffold for platelet adhesion.ConclusioncfDNA was increased in EGPA, associated with disease activity. The presence of DNase-resistant EETs in small-vessel thrombi might contribute to higher concentration of cfDNA and the occurrence of immunothrombosis in EGPA.

scholarly journals Increased circulating cell-free DNA in eosinophilic granulomatosis with polyangiitis: implications for eosinophil extracellular traps and immunothrombosis

2021 ◽  
Author(s):  
Teppei Hashimoto ◽  
Shigeharu Ueki ◽  
Yosuke Kamide ◽  
Yui Miyabe ◽  
Mineyo Fukuchi ◽  
...  
Keyword(s):  
Disease Activity ◽  
Clinical Significance ◽  
Platelet Adhesion ◽  
Granulomatosis With Polyangiitis ◽  
Eosinophilic Granulomatosis With Polyangiitis ◽  
Tissue Samples ◽  
Extracellular Traps ◽  
Free Dna ◽  
Eosinophilic Granulomatosis

Background: Endogenous DNA derived from nuclei or mitochondria is released into the blood circulation as cell-free DNA (cfDNA) following cell damage or death. cfDNA is associated with various pathological conditions; however, its clinical significance in antineutrophil cytoplasmic antibody-associated vasculitis (AAV) remains unclear. This study aimed to evaluate the clinical significance of cfDNA in AAV. Methods: We enrolled 35 patients with AAV, including 10 with eosinophilic granulomatosis with polyangiitis (EGPA), 13 with microscopic polyangiitis, and 12 with granulomatosis with polyangiitis. Serum cf-nuclear DNA (cf-nDNA) and cf-mitochondrial DNA (cf-mtDNA) levels were measured by quantitative polymerase chain reaction. Tissue samples from EGPA patients were examined by immunofluorescence and transmission electron microscopy. The structure, stability, and platelet adhesion of eosinophil extracellular traps (EETs) were also assessed in vitro. Results: Serum cf-nDNA and cf-mtDNA levels were significantly higher in AAV than in healthy controls, with the highest levels in EGPA; however, serum DNase activities were comparable among all groups. cf-nDNA and cf-mtDNA decreased after treatment and were associated with disease activity only in EGPA. Blood eosinophil count and plasma D-dimer levels were significantly correlated with cf-nDNA in EGPA and cf-mtDNA. EGPA tissue samples showed lytic eosinophils and EETs in small-vessel thrombi. EETs showed greater stability against DNase than neutrophil extracellular traps and provided a scaffold for platelet adhesion in vitro. Conclusion: cfDNA was increased in EGPA, associated with disease activity. The presence of DNase-resistant EETs might contribute to the occurrence of immunothrombosis in EGPA.

scholarly journals Biological therapy improves myocarditis and disease activity in eosinophilic granulomatosis with polyangiitis patients

2020 ◽  
Author(s):  
Chrong-Reen Wang ◽  
Yi-Shan Tsai ◽  
Jiu-Yao Wang ◽  
Hung-Wen Tsai ◽  
Cheng-Han Lee
Keyword(s):  
Retrospective Study ◽  
Disease Activity ◽  
Cardiac Dysfunction ◽  
Granulomatosis With Polyangiitis ◽  
Biological Therapy ◽  
Cardiac Insufficiency ◽  
Eosinophilic Granulomatosis With Polyangiitis ◽  
Heart Involvement ◽  
Eosinophilic Granulomatosis ◽  
Eosinophil Counts

Abstract Background Cardiac insufficiency is a major cause of mortality in eosinophilic granulomatosis with polyangiitis (EGPA). Despite the dosages-related cardiotoxicity, cyclophosphamide is usually prescribed to induce disease remission in the presence of myocarditis with heart involvement. There is an imperative need of novel medications to efficiently control disease activity and spare the use of cyclophosphamide. Methods A retrospective study was carried out in hospitalized EGPA patients from January 1, 2008 to December 31, 2019, focusing on the use of biologics including benralizumab (BEN, anti-IL-5 receptor), mepolizumab (MEP, anti-IL-5), omalizumab (OMA, anti-IgE) and rituximab (RTX, anti-CD20). Results Sixteen admitted patients, 8 females aged 10 to 70 years (40.4 ± 15.5), had higher disease activities (Birmingham Vasculitis Activity Score 16 to 39, 26.8 ± 6.9), poorer prognostic factors (five-factor score 1 or 2, 1.4 ± 0.5) and elevated eosinophil counts (2,314 to 26,781/µL, 11,108 ± 7,060). BEN, MEP, OMA and RTX were prescribed in one, 2, one and 6 patients, respectively. Ten patients (63%) had myocarditis with impaired left ventricle ejection fraction and cardiac arrhythmia, and 7 received biological therapy without a combined use of cyclophosphamide. One patient obtained MEP with a 100 mg quadri-weekly × 13 regimen at induction for disease relapse. Six patients acquired RTX with a 375 mg/m2 weekly × 4 regimen at induction for refractory activity or relapsing disease, or plus a yearly maintenance schedule in 5. All patients received serial cardiac magnetic resonance imaging, transthoracic echocardiography and 24-hour Holter monitor to evaluate the therapeutic responses in heart involvement. After biological therapy, there were improved cardiac dysfunction, lower eosinophil counts and clinical remission (4 complete, 3 partial) with a relapse-free follow-up (13 to 61 months, 39.1 ± 16.0) after induction. Conclusions In this single-center retrospective study, we observed improved cardiac dysfunction and disease activity after biological therapy in EGPA patients with myocarditis.

Innate immune response reflects disease activity in eosinophilic granulomatosis with polyangiitis

2018 ◽  
Vol 48 (10) ◽  
pp. 1305-1316 ◽  
Author(s):  
Naomi Tsurikisawa ◽  
Chiyako Oshikata ◽  
Maiko Watanabe ◽  
Takahiro Tsuburai ◽  
Takeshi Kaneko ◽  
...  
Keyword(s):  
Immune Response ◽  
Disease Activity ◽  
Innate Immune Response ◽  
Granulomatosis With Polyangiitis ◽  
Innate Immune ◽  
Eosinophilic Granulomatosis With Polyangiitis ◽  
Eosinophilic Granulomatosis

scholarly journals Cardiac Involvement in Eosinophilic Granulomatosis With Polyangiitis: A Retrospective Study in the Chinese Population

2020 ◽  
Vol 7 ◽  
Author(s):  
Yingying Chen ◽  
Xiaoxiao Guo ◽  
Jiaxin Zhou ◽  
Jing Li ◽  
Qingjun Wu ◽  
...  
Keyword(s):  
Disease Activity ◽  
Eosinophil Count ◽  
Chinese Population ◽  
Cardiac Involvement ◽  
Granulomatosis With Polyangiitis ◽  
Age At Onset ◽  
Eosinophilic Granulomatosis With Polyangiitis ◽  
Appropriate Treatment ◽  
Younger Age ◽  
Eosinophilic Granulomatosis

Introduction: Cardiac involvement in eosinophilic granulomatosis with polyangiitis (EGPA) is associated with a poor prognosis and high mortality; however, few studies about cardiac involvement in EGPA in the Chinese population are available. We conducted this study to determine the clinical characteristics and overall outcomes of Chinese EGPA patients with cardiac involvement.Materials and Methods: We retrospectively collected the clinical data of 83 patients diagnosed with EGPA and analyzed the differences between the patients with and without cardiac involvement.Results: The prevalence of cardiac involvement in EGPA in this cohort was 27.7%. Compared with those without cardiac involvement, EGPA patients with cardiac involvement tended to have a younger age at onset (mean ± SD: 38.4 ± 10.5 vs. 42.1 ± 15.9 years, respectively, p = 0.039), higher eosinophil count (median [IQR]: 5810 [4020–11090] vs. 2880 [1530–6570] n/μL, respectively, p = 0.004), higher disease activity assessed using the Birmingham vasculitis activity score (BVAS) (median [IQR]: 20 [16–28] vs. 15 [12–18], respectively, p = 0.001), and poorer prognosis (Five Factor Score [FFS] ≥ 1: 100% vs. 38.3%, respectively, p = 0.001). In the cardiac involvement group, 43.5% of patients were asymptomatic, but cardiac abnormalities could be detected by cardiac examinations. With appropriate treatment, the overall outcomes of EGPA patients with cardiac involvement in our cohort were good, with only 3 (13.0%) patients dying in the acute phase and no patients dying during follow-up.Conclusions: Cardiac involvement in EGPA was associated with a younger age at onset, higher eosinophil count, higher disease activity, and a poorer prognosis. Comprehensive cardiac examinations and appropriate treatment are essential to improve the prognosis of those with cardiac involvement.

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